Background: Electrophysiological techniques allowed identification of sub-clinical pathological changes and early diagnosis of diabetic peripheral neuropathy (PN). Neopterin is a marker of inflammation and cellular immune response that is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (PN) is associated with inflammatory/immune processes and therefore, we hypothesized that neopterin could be used as a marker of neuropathy in type 1 diabetes mellitus (T1DM).
Objectives: To measure neopterin levels in 60 children and adolescents with type 1 diabetes mellitus (T1DM) compared with 30 age- and sex-matched healthy controls and to assess its possible relation to glycemic control, PN and nerve conduction studies (NCS).
Methods: Sixty patients ≤18 years and >5 years disease duration were subjected to neurological assessment by neuropathy disability score (NDS) and NCS for median, ulnar, posterior tibial and common peroneal nerves. Mean fasting blood glucose, lipid profile, HbA1c, high sensitivity C-reactive protein (hs-CRP) and serum neopterin levels by enzyme linked immunosorbent assay were measured.
Results: The frequency of PN according to NDS was 40 (66.7%) patients out of 60, while NCS confirmed that 30 (50%) patients had this complication. Neopterin levels were significantly higher in patients with DPN than those without (median (IQR), 53.5 (35 60) nmol/l vs 17 (13 32) nmol/l) and healthy controls (5.0 (3.2 7.0) nmol/l) (P<0.001). Significant positive correlations were found between neopterin levels and HbA1c (r=0.560, P=0.005), serum creatinine (r=0.376, P=0.003), total cholesterol (r=0.405, P=0.026) and hs-CRP (r=0.425, P=0.012) among patients with DPN. Neopterin levels were positively correlated to motor latency of tibial and common peroneal nerves as well as motor and sensory latencies of median and ulnar nerves. Logistic regression analysis revealed that neopterin was a significant independent variable related to DN (Odds ratio, 2.976). According to ROC curve analysis, neopterin cutoff value 32 nmol/l could differentiate patients with and without DPN with 100% sensitivity and 96.7% specificity.
Conclusions: Diabetic peripheral neuropathy occur in both sensory and motor nerves in children and adolescents with T1DM, even before the presence of symptoms. Nerve conduction changes in lower limbs are more common than that in the upper extremities.The strong relation between neopterin and nerve conduction parameters supports its use as a reliable serum biomarker for PN in T1DM.Our study highlights the role of inflammation and cellular immune activation in the pathophysiology of diabetic neuropathy and introduces neopterin as a future therapeutic target.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology